ANALGESIC ACTIVITY OF COMPLEX OF O-BENZOYLOXIME OF 3,7-DIAZABICYCLO[3.3.1]NONAN-9-ONE WITH -CYCLODEXTRIN

Abstract

Introduction. Pain syndrome is the most common phenomenon in medical practice. Despite the variety of drugs availability, the search for new highly effective analgesics for pain management remains the most important goal. The purpose of the work: directed synthesis of potential biological active diazabicyclononanone series compounds based on 1-(2-ethoxyethyl)piperidin-4-one, modifying the structure of diazabicyclononanone with various pharmacophore functional groups and determining their biological properties. Results and discussions: 3-(2-Ethoxyethyl)-7-cyclopropanemethyl-3,7-diazabicyclo[3.3.1]nonan-9-one have been synthesized by Mannich reaction of 1-(2-ethoxyethyl)piperidin-4-one with the primary amine 3-cyclopropylmethylamine and paraform in glacial acetic acid and methanol. In order to obtain a compound with pharmacological activity 3,7-diazabicyclononanone have been obtained out by the Huang-Minlon reduction reaction, and as a result, 3-(2-ethoxyethyl)-7-cyclopropanemethyl-3,7-diazabicyclo[3.3.1]nonane was isolated with a yield of 74.2 %. Oxymylation of 3,7-diazabicyclononanone was carried out by heating in the presence of pyridine and hydroxylamine hydrochloride in ethyl alcohol for 20-25 h. Synthesised oxime after heating with benzoyl chloride in the presence of absolute benzene for 6-7 h led to O-benzoyloxime. Encapsulation of O-benzoyloxime was resolved using b-cyclodextrin. As a result, an amorphous powder complex was obtained. Structure and composition of newly synthesized 3-(2-ethoxyethyl)-7-cyclopropanemethyl-3,7-diazabicyclo[3.3.1]nonan-9-one, bispidine, oxime and O-benzoyloxime clarified with the help of methods as IR, ¹³C and ¹H NMR spectroscopy and elemental analysis. Conclusion: Biological activity of complex of O-benzoyloxime of 3-(2-ethoxyethyl)-7-cyclopropylmethyl-3,7-diazabicyclo[3.3.1]nonan-9-one with b-cyclodextrin with laboratory code NA-332 has been studied at the Institute of General Genetics and Cytology. As a result of biological screening, it was found that the complex of O-benzoyloxime of 3-(2-ethoxyethyl)-7-cyclopropylmethyl-3,7-diazabicyclo[3.3.1]nonan-9-one with b-cyclodextrin shows higher analgesic activity than tramal and has complete analgesia. The results of studies determine the acute toxicity of HA-332 lower than tramal.